Solution structure of Escherichia coli Par10: The prototypic member of the Parvulin family of peptidyl‐prolyl cis/trans isomerases

E. coli Par10 is a peptidyl‐prolyl cis/trans isomerase (PPIase) from Escherichia coli catalyzing the isomerization of Xaa‐Pro bonds in oligopeptides with a broad substrate specificity. The structure of E. coli Par10 has been determined by multidimensional solution‐state NMR spectroscopy based on 1207 conformational constraints (1067 NOE‐derived distances, 42 vicinal coupling‐constant restraints, 30 hydrogen‐bond restraints, and 68 ϕ/ψ restraints derived from the Chemical Shift Index). Simulated‐annealing calculations with the program ARIA and subsequent refinement with XPLOR yielded a set of 18 convergent structures with an average backbone RMSD from mean atomic coordinates of 0.50 Å within the well‐defined secondary structure elements. E. coli Par10 is the smallest known PPIase so far, with a high catalytic efficiency comparable to that of FKBPs and cyclophilins. The secondary structure of E. coli Par10 consists of four helical regions and a four‐stranded antiparallel β‐sheet. The N terminus forms a β‐strand, followed by a large stretch comprising three α‐helices. A loop region containing a short β‐strand separates these helices from a fourth α‐helix. The C terminus consists of two more β‐strands completing the four‐stranded anti‐parallel β‐sheet with strand order 2143. Interestingly, the third β‐strand includes a Gly‐Pro cis peptide bond. The curved β‐strand forms a hydrophobic binding pocket together with α‐helix 4, which also contains a number of highly conserved residues. The three‐dimensional structure of Par10 closely resembles that of the human proteins hPin1 and hPar14 and the plant protein Pin1At, belonging to the same family of highly homologous proteins.